CN110787261A - Ointment for clearing heat, cooling blood, stopping bleeding, relieving swelling and promoting wound healing and preparation method thereof - Google Patents

Abstract

The invention discloses an ointment for clearing heat and cooling blood, stopping bleeding and reducing swelling and promoting wound healing and a preparation method thereof, and the ointment comprises the following raw materials: rhubarb, coptis, pseudo-ginseng, angelica dahurica, donkey-hide gelatin, calcined dragon bone, rhizoma bletillae, myrrh, cuttlebone, madder, dragon's blood, pearl, borneol and liquorice. The invention has good curative effect on various skin traumatic hemorrhage, ulcer, fester and the like, has short treatment period and greatly relieves the pain and economic burden of patients. The medicine directly acts on the affected part, improves the absorption efficiency of the medicine, promotes the bleeding point and the ulcer surface to heal quickly, has quick curative effect, short treatment course, is a pure traditional Chinese medicine preparation, has no toxic or side effect, wide and easily available medicine sources, convenient application, small dosage, no pain and no relapse after healing, and is applied to the affected part.

Description

Ointment for clearing heat, cooling blood, stopping bleeding, relieving swelling and promoting wound healing and preparation method thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an ointment for clearing heat, cooling blood, stopping bleeding, relieving swelling and promoting wound healing and a preparation method thereof.

Background

Traumatic hemorrhage, metrorrhagia and metrostaxis, hematemesis and hematochezia are frequently encountered diseases and difficult diseases in the blood syndrome of traditional Chinese medicine. There is data display. The incidence rate of hematemesis and hematochezia is more than 12%, which is more common in young and strong men than women. The Zhikang capsule is a unique product in the Qian standing grain pharmaceutical industry, has good clinical effect since the sale, and consists of the following components in a prescription: rhubarb, coptis, angelica dahurica, liquorice, madder, donkey-hide gelatin, pseudo-ginseng, rhizoma bletillae, pearl, calcined dragon bone, vinegar myrrh, cuttlebone, dragon's blood and borneol, wherein the total 14 medicines are selected; the functional indications are as follows: clear heat, cool blood, stop bleeding, remove blood stasis, promote granulation and relieve pain. Can be used for treating traumatic hemorrhage, metrorrhagia, hematemesis, hematochezia, etc. However, because it is an oral preparation, patients are reluctant to take oral drugs when traumatic bleeding occurs, and the existing external hemostatic drugs generally have the problems of small wound attached dose, easy falling off, slow hemostasis, slow wound healing, scar and pigmentation after healing and the like. Therefore, in order to overcome the defects of the prior preparation formulation, the invention particularly discloses an external ointment preparation for stopping bleeding, reducing swelling, diminishing inflammation and promoting wound healing.

Disclosure of Invention

The invention provides an ointment which has good curative effects on various skin traumatic hemorrhage, skin mucosa ulcer and fester and the like, and has the functions of clearing heat and cooling blood, stopping bleeding and diminishing swelling and promoting wound healing and a preparation method thereof.

In order to achieve the purpose of the invention, the technical scheme is as follows:

an ointment for clearing heat, cooling blood, stopping bleeding, diminishing swelling and promoting wound healing is prepared from 5-15g of medicinal dry paste powder and 5-11g of thickening agent, 15-20g of oil phase matrix, 10-20g of water phase matrix, 20-30g of surfactant, 0.1-0.5 part of preservative and the balance of water in each 100g of the ointment.

Preferably, the medicine dry paste powder comprises, by weight, 50-80 parts of rheum officinale, 40-60 parts of coptis chinensis, 40-60 parts of pseudo-ginseng, 20-40 parts of angelica dahurica, 40-60 parts of donkey-hide gelatin, 30-55 parts of calcined keel, 30-55 parts of rhizoma bletillae, 20-40 parts of vinegar myrrh, 30-55 parts of cuttlebone, 40-60 parts of madder, 10-20 parts of dragon's blood, 2-10 parts of pearl, 2-10 parts of borneol and 5-20 parts of liquorice, and each 100g of the ointment comprises, by weight, 5-15g of medicine dry paste powder, 1-3g of chitosan derivative, 4-8g of β -sodium glycerophosphate, 15-20g of isopropyl myristate, 10-20g of polyethylene glycol 400 or glycerol, 5-20g of tween 8015-20g, 5-10g of polyoxyethylene castor oil, 0.1-0.5 part of ethyl p-hydroxybenzoate and the balance water.

Preferably, the medicine comprises the following components in parts by weight: 65 parts of rhubarb, 50 parts of coptis chinensis, 50 parts of pseudo-ginseng, 31 parts of angelica dahurica, 50 parts of donkey-hide gelatin, 44 parts of calcined dragon bone, 44 parts of rhizoma bletillae, 31 parts of vinegar myrrh, 44 parts of cuttlebone, 50 parts of madder, 12 parts of dragon's blood, 4 parts of pearl, 4 parts of borneol and 11 parts of liquorice.

Preferably, the chitosan derivative may be one or a mixture of more than one of chitosan lactate, chitosan hydrochloride, chitosan nitride, carboxymethyl chitosan, hydroxypropyl chitosan, chitosan acetate, chitosan propionate, chitosan succinate, chitosan glutarate, chitosan adipate, succinylated chitosan and maleylated chitosan.

Furthermore, the medicinal dry paste powder consists of dry paste powder, superfine powder, donkey-hide gelatin and borneol, and comprises the following steps:

1) mixing radix et rhizoma Rhei, Coptidis rhizoma, Notoginseng radix and radix Angelicae Dahuricae, adding 5-10 times of 70-85% ethanol, and soaking for 45-60 min; heating and refluxing the soaked mixture twice, wherein each time lasts for 1.5-3 hours, combining the alcohol extract, and filtering through a 200-mesh stainless steel net to obtain a filtrate for later use; adding 8-10 times of water into the dregs of the alcohol extraction, cuttlebone, bletilla striata, calcined dragon bone, madder and liquorice, decocting for 2 times, each time for 1-1.5 hours, combining the decoctions, filtering through a 180-mesh stainless steel net, concentrating the filtrate to obtain clear paste with the relative density of 1.05-1.10, spray drying or reduced pressure concentration drying, and crushing into 120-mesh 180-mesh dispersed fine powder to obtain dry paste powder;

2) mixing Myrrha, Margarita and sanguis Draxonis, pulverizing, sieving with 100 mesh sieve to obtain coarse powder, micronizing, and sieving with 300 mesh sieve to obtain superfine powder with average particle diameter of 50 μm or less;

3) taking colla Corii Asini, pulverizing, and sieving with 100 mesh sieve; grinding Borneolum Syntheticum into fine powder for use.

The invention also provides a preparation method of the ointment, which is characterized by comprising the following steps:

1) dissolving polyethylene glycol 400 or glycerol in water, adding chitosan derivative, stirring to dissolve, dissolving β -sodium glycerophosphate in distilled water, stirring to dissolve, dropwise adding the above chitosan solution, continuously stirring and fully mixing, standing until bubbles disappear, then adding ethyl p-hydroxybenzoate, fully mixing with the dried extract powder at constant temperature of 85 ℃, stirring to dissolve, and adding water to the prescription amount to serve as a water phase;

2) mixing the above superfine powder with isopropyl myristate, and mixing at constant temperature of 75-90 deg.C to obtain oil phase;

3) adding tween 80 and polyoxyethylene castor oil into the oil phase, stirring, dissolving, slowly adding the water phase while stirring, grinding Borneolum with small amount of 95% ethanol, dissolving, adding into the matrix, stirring, cooling, and adding water to 100g to obtain cream.

And (3) composition analysis:

the invention relates to an external preparation developed on the basis of a Zhikang capsule, which has an unexpected technical effect on various skin traumatic hemorrhages and skin mucosa ulcer fester. In the formula, the rhubarb and the coptis are used as monarch drugs for clearing heat, cooling blood, stopping bleeding, removing blood stasis, dissipating stagnation and activating stagnancy; the rhubarb is bitter and cold, so that the heat toxin can be cleared away; it can also be used for treating bleeding due to blood stasis accumulation, new blood failing to grow, and blood failing to enter meridians; the rhubarb has the functions of diminishing inflammation, resisting bacteria and promoting tissue repair; huang Lian is bitter and cold in property and special for purging fire, removing toxicity, clearing heat and drying dampness, so it is indicated for heat-toxicity due to intense heat, drying dampness and astringing ulcer, and combined with Da Huang, which is the main one in the recipe. Pseudo-ginseng, dragon's blood, angelica dahurica, donkey-hide gelatin and madder are ministerial drugs in the formula, wherein the pseudo-ginseng has the characteristics of removing blood stasis and stopping bleeding, stopping bleeding without remaining blood stasis, and has the effects of removing blood stasis and stopping bleeding, relieving swelling and pain, resisting inflammation and repairing mucous membrane; radix Rubiae is cold in nature and enters blood system, and has effects of cooling blood and stopping bleeding, and removing blood stasis; the dragon's blood is sweet and salty, and the salty taste is specially used for blood, so that the blood circulation can be promoted, stasis can be removed and pain can be relieved by oral administration, the wonderful use of stopping bleeding without stasis can be realized, the angelica dahurica can dispel wind, eliminate dampness, reduce swelling, expel pus and relieve pain, the powder can be dissipated for patients without ulceration, and the powder can expel pus and relieve pain for patients with ulceration; the donkey-hide gelatin not only enriches blood and nourishes yin, moistens dryness and stops bleeding, but also has the efficacy of removing necrosis and promoting granulation, and treats carbuncle, sore and ulcer. The cuttlebone, calcined dragon bone, rhizoma bletillae, myrrh, pearl and borneol belong to the category of the prescription and are used as adjuvant drugs in the prescription. Myrrha has effects of promoting blood circulation, activating qi-flowing, relieving pain, detumescence and promoting granulation, can be used for treating various pains caused by internal and external stasis, and carbuncle, cellulitis, swelling and pain, and has antiinflammatory, analgesic, antipyretic, astringent, and antibacterial effects. Hai Piao Xiao astringes to stop bleeding, Gu Long calcined to astringe dampness and heal wound, it is combined with Bai Zhi and Bing pian to treat ulcer with pus; bletilla striata has effects of astringing, stopping bleeding, relieving swelling and promoting granulation, and bletilla striata glue contained in the product forms a layer of protective film on injured wound surface to protect wound surface and promote granulation tissue growth of wound surface; the pearl and the borneol have the effects of clearing heat, relieving pain, removing necrotic tissue, promoting granulation, cooling the wound surface, relieving pain and treating the patients with chronic ulcer and unhealed wound. The six medicines are combined, so that the effects of purging fire, removing toxicity, clearing heat and drying dampness are enhanced by assisting monarch and minister medicines, and the pain caused by skin ulcer is treated at the same time. As for the guiding drug in the recipe, gan Cao is sweet and neutral and enters spleen and stomach meridians, it has the actions of relieving spasm and pain, moderating property of herbs, guiding herbs to enter meridians, and it is combined with Da Huang to moderate its purgative action. The recipe is composed of fourteen Chinese herbs, and the monarch, minister, assistant and guide herbs are matched to achieve the effects of clearing heat, cooling blood and stopping bleeding, and dispersing blood stasis, relieving pain and astringing. The whole formula focuses on hemostasis without stasis retention and blood stasis removal without blood movement so as to achieve the effects of clearing heat and drying dampness, removing blood stasis and promoting granulation and relieving pain, and is used for treating various fester and pain caused by skin traumatic hemorrhage and skin mucosa ulcer canker, and no new muscle generation, so that the medicine can clear heat and toxin, remove blood stasis, promote pus and eliminate sore, relieve pain and blood stasis, regulate qi and blood, and promote new muscle generation.

Compared with the prior art, the invention has the following beneficial technical effects:

1) the invention has good curative effect on various skin traumatic hemorrhage, skin mucosa ulcer and ulceration and the like, has short treatment period and greatly relieves the pain and economic burden of patients. The invention has better effect of promoting the healing of the ulcer wound surface by combining the medicines and using the 14 medicines with the pharmacological effects of clearing heat, stopping bleeding, promoting blood circulation, removing blood stasis, removing necrotic tissue, promoting granulation, relieving swelling, alleviating pain and the like, has the advantages of short recovery period and no scar after the wound is healed, and has practical and reliable curative effect. Directly acting on affected part, avoiding first pass effect of medicine, improving absorption efficiency of medicine, promoting ulcer healing, stopping bleeding time, and has advantages of short treatment course, pure Chinese medicinal preparation, no adverse side effect, wide and easily available medicine source, convenient application, external application on affected part, small dosage, no pain, and no recurrence after healing. The invention has the advantages of no foreign body sensation, strong adhesiveness at the pathological change part, no irritation to skin mucous membrane, no pollution to clothes, convenient application, uniformity, fineness, no greasy feeling, high transdermal absorption speed and the like.

2) The invention takes Tween 80 and polyoxyethylene hydrogenated castor oil as emulsifier, polyethylene glycol 400 or glycerol as auxiliary emulsifier, isopropyl palmitate as oil phase, aqueous solution of chitosan derivative and β -sodium glycerophosphate as water phase, ethyl p-hydroxybenzoate as preservative, the prepared oil-in-water type emulsifiable paste has uniform and fine appearance, is easy to spread and has no greasy feeling.

3) The external preparation has the double advantages of emulsifiable paste and in-situ gel, can improve the solubility, transdermal rate and targeting effect of the medicament, and can reduce the irritation of the medicament; the ointment is used in a package in a solution state, and then a phase transition mixed solution (phase transition temperature of 32-38 ℃) is generated at an application part immediately after the ointment is used in the package in the solution state, the mixed solution can be solidified into gel, and a non-chemical cross-linked semisolid preparation is formed, has good biological adhesion, strong affinity with the application part, particularly skin and mucous membrane tissues, long retention time, within 3 minutes of gelling time and good mechanical strength, can obviously improve the curative effect, increases the compliance of a patient, and has the advantages of simple preparation, convenient use, easy control of dosage and the like.

Detailed Description

In order that the above objects, features and advantages of the present invention may be more clearly understood, the present invention will be described in detail below with reference to specific embodiments. It should be noted that the embodiments and features of the embodiments of the present application may be combined with each other without conflict.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

Example 1:

the raw material medicine comprises the following components: 50 parts of rhubarb, 40 parts of coptis chinensis, 40 parts of pseudo-ginseng, 20 parts of angelica dahurica, 40 parts of donkey-hide gelatin, 30 parts of calcined dragon bone, 30 parts of rhizoma bletillae, 20 parts of vinegar myrrh, 30 parts of cuttlebone, 40 parts of madder, 10 parts of dragon's blood, 2 parts of pearl, 2 parts of borneol and 5 parts of liquorice.

The ointment formula comprises, per 100g, 5g of medicinal dry paste powder, 1g of chitosan hydrochloride, 8g of β -sodium glycerophosphate, 15g of isopropyl myristate, 10g of polyethylene glycol 40010g, 5g of tween 8015g of polyoxyethylene castor oil, 0.1 part of ethyl p-hydroxybenzoate and 41g of water.

The preparation process of the medicine dry paste powder comprises the following steps: consists of dry paste powder, superfine powder, donkey-hide gelatin and borneol, and comprises the following steps:

(1) mixing radix et rhizoma Rhei, Coptidis rhizoma, Notoginseng radix and radix Angelicae Dahuricae, adding 5 times of 70 ethanol, and soaking for 45 min; heating and refluxing the soaked mixture twice, wherein each time lasts for 1.5 hours, combining the alcohol extract, and filtering through a stainless steel mesh of 200 meshes to obtain a filtrate for later use; adding 8 times of water into the dregs of the alcohol extraction, cuttlebone, bletilla striata, calcined dragon bone, madder and liquorice, decocting for 2 times, 1 hour each time, combining the decoction, filtering through a stainless steel net with 200 meshes for 180 meshes, concentrating the filtrate to obtain clear paste with the relative density of 1.05-1.10, carrying out spray drying or reduced pressure concentration drying, crushing to obtain dispersed fine powder with 180 meshes for 120 meshes, and preparing dry paste powder;

(2) mixing Myrrha, Margarita and sanguis Draxonis, pulverizing, sieving with 100 mesh sieve to obtain coarse powder, micronizing, and sieving with 300 mesh sieve to obtain superfine powder with average particle diameter of 50 μm or less;

(3) taking colla Corii Asini, pulverizing, and sieving with 100 mesh sieve; grinding Borneolum Syntheticum into fine powder for use.

The preparation method of the ointment comprises the following steps:

1) dissolving polyethylene glycol 400 or glycerol in water, adding chitosan derivative, stirring to dissolve, dissolving β -sodium glycerophosphate in distilled water, stirring to dissolve, dropwise adding the above chitosan solution, continuously stirring and fully mixing, standing until bubbles disappear, then adding ethyl p-hydroxybenzoate, fully mixing with the dried extract powder at constant temperature of 85 ℃, stirring to dissolve, and adding water to the prescription amount to serve as a water phase;

2) mixing the above superfine powder with isopropyl myristate, and mixing at constant temperature of 75-90 deg.C to obtain oil phase;

3) adding tween 80 and polyoxyethylene castor oil into the oil phase, stirring, dissolving, slowly adding the water phase while stirring, grinding Borneolum with small amount of 95% ethanol, dissolving, adding into the matrix, stirring, cooling, and adding water to 100g to obtain cream.

Example 2

The raw material medicine comprises the following components: 80 parts of rhubarb, 60 parts of coptis chinensis, 60 parts of pseudo-ginseng, 40 parts of angelica dahurica, 60 parts of donkey-hide gelatin, 55 parts of calcined dragon bone, 55 parts of rhizoma bletillae, 40 parts of vinegar myrrh, 55 parts of cuttlebone, 60 parts of madder, 20 parts of dragon's blood, 10 parts of pearl, 10 parts of borneol and 20 parts of liquorice.

The ointment formula comprises, per 100g, 15g of medicinal dry extract powder, 3g of carboxymethyl chitosan, 4g of β -sodium glycerophosphate, 20g of isopropyl myristate, 20g of glycerol, 8020g of tween, 10g of polyoxyethylene castor oil, 0.5 part of ethyl p-hydroxybenzoate and 11.5g of water in balance.

The preparation process of the medicine dry paste powder comprises the following steps: consists of dry paste powder, superfine powder and borneol, and comprises the following steps:

(1) mixing the rhubarb, the coptis root, the pseudo-ginseng and the angelica dahurica, and adding 10 times of 85% ethanol for soaking for 60 minutes; heating and refluxing the soaked mixture twice, each time for 3 hours, combining the alcohol extract, filtering through a stainless steel mesh of 200 meshes, and keeping the filtrate for later use; adding 8-10 times of water into the dregs of the alcohol extraction, cuttlebone, bletilla striata, calcined dragon bone, madder and liquorice, decocting for 2 times, each time for 1.5 hours, combining the decoctions, filtering through a 180-mesh stainless steel net, concentrating the filtrate to obtain clear paste with the relative density of 1.05-1.10, carrying out spray drying or reduced pressure concentration drying, and crushing to obtain 120-mesh 180-mesh dispersed fine powder to obtain dry paste powder;

(2) mixing Myrrha, Margarita and sanguis Draxonis, pulverizing, sieving with 100 mesh sieve to obtain coarse powder, micronizing, and sieving with 300 mesh sieve to obtain superfine powder with average particle diameter of 50 μm or less;

(3) taking colla Corii Asini, pulverizing, and sieving with 100 mesh sieve; grinding Borneolum Syntheticum into fine powder for use.

The preparation method of the ointment comprises the following steps:

1) dissolving polyethylene glycol 400 or glycerol in water, adding chitosan derivative, stirring to dissolve, dissolving β -sodium glycerophosphate in distilled water, stirring to dissolve, dropwise adding the above chitosan solution, continuously stirring and fully mixing, standing until bubbles disappear, then adding ethyl p-hydroxybenzoate, fully mixing with the dried extract powder at constant temperature of 85 ℃, stirring to dissolve, and adding water to the prescription amount to serve as a water phase;

2) mixing the above superfine powder with isopropyl myristate, and mixing at constant temperature of 75-90 deg.C to obtain oil phase;

3) adding tween 80 and polyoxyethylene castor oil into the oil phase, stirring, dissolving, slowly adding the water phase while stirring, grinding Borneolum with small amount of 95% ethanol, dissolving, adding into the matrix, stirring, cooling, and adding water to 100g to obtain cream.

Example 3

The raw material medicine comprises the following components: 65 parts of rhubarb, 50 parts of coptis chinensis, 50 parts of pseudo-ginseng, 31 parts of angelica dahurica, 50 parts of donkey-hide gelatin, 44 parts of calcined dragon bone, 44 parts of rhizoma bletillae, 31 parts of vinegar myrrh, 44 parts of cuttlebone, 50 parts of madder, 12 parts of dragon's blood, 4 parts of pearl, 4 parts of borneol and 11 parts of liquorice.

The ointment formula comprises, per 100g, 10g of medicinal dry extract powder, 1.5g of chitosan hydrochloride, 6g of β -sodium glycerophosphate, 18g of isopropyl myristate, 15g of glycerol, 8018g of tween, 7.5g of polyoxyethylene castor oil, 0.25 part of ethyl p-hydroxybenzoate and 24g of water.

The preparation process of the medicine dry paste powder comprises the following steps: consists of dry paste powder, superfine powder, donkey-hide gelatin and borneol, and comprises the following steps:

(1) mixing the rhubarb, the coptis root, the pseudo-ginseng and the angelica dahurica, and adding 8 times of 80% ethanol for soaking for 45 minutes; heating and refluxing the soaked mixture twice, each time for 2 hours, combining the alcohol extract, filtering through a stainless steel mesh of 200 meshes, and keeping the filtrate for later use; adding 10 times of water into the dregs of the alcohol extraction and cuttlebone, bletilla striata, calcined dragon bone, madder and liquorice, decocting for 2 times, 1 hour each time, combining the decoction, filtering through a stainless steel net with 200 meshes for 180 meshes, concentrating the filtrate to obtain clear paste with the relative density of 1.05-1.10, spray drying or reduced pressure concentration drying, crushing to obtain dispersed fine powder with 180 meshes for 120 meshes, and preparing dry paste powder;

(2) mixing Myrrha, Margarita and sanguis Draxonis, pulverizing, sieving with 100 mesh sieve to obtain coarse powder, micronizing, and sieving with 300 mesh sieve to obtain superfine powder with average particle diameter of 50 μm or less;

(3) taking colla Corii Asini, pulverizing, and sieving with 100 mesh sieve; grinding Borneolum Syntheticum into fine powder for use.

The preparation method of the ointment comprises the following steps:

1) dissolving polyethylene glycol 400 or glycerol in water, adding chitosan derivative, stirring to dissolve, dissolving β -sodium glycerophosphate in distilled water, stirring to dissolve, dropwise adding the above chitosan solution, continuously stirring and fully mixing, standing until bubbles disappear, then adding ethyl p-hydroxybenzoate, fully mixing with the dried extract powder at constant temperature of 85 ℃, stirring to dissolve, and adding water to the prescription amount to serve as a water phase;

2) mixing the above superfine powder with isopropyl myristate, and mixing at constant temperature of 75-90 deg.C to obtain oil phase;

3) adding tween 80 and polyoxyethylene castor oil into the oil phase, stirring, dissolving, slowly adding the water phase while stirring, grinding Borneolum with small amount of 95% ethanol, dissolving, adding into the matrix, stirring, cooling, and adding water to 100g to obtain cream.

Example 4: experiment on moldability of cream preparation

According to the quality requirements of the cream, the quality of the cream prescription is considered from the aspects of appearance shape, value, stability, irritation and the like.

1) Examination of appearance Properties

Appearance: the cream has brownish red color, uniform texture, no oil-water separation, and borneol fragrance.

Spreadability: it can be easily applied to skin or mucosa.

Fineness is as follows: the cream was uniform, applied to the hands without grit, and a thin layer of cream was applied to the glass plate without visible individual particles or air bubbles. See table for details.

Washing removal performance: uniformly smearing 5g of matrix on a glass plate with an area of 10cm × 10cm, applying gauze with a corresponding area on the surface of the matrix to make the gauze fully contact with the preparation, and washing with tap water at a fixed flow rate after 24h to completely remove the matrix in a short time.

pH value: the pH value of the cream is preferably close to that of human body, the pH value of the W/O type matrix is required to be not more than 8.5, and the pH value of the O/W type matrix is required to be not more than 8.3. The method comprises the following steps: taking a sample, adding distilled water for dilution, uniformly stirring, standing to obtain a uniform emulsion, and measuring the pH value of the cream by using a pH meter.

And (3) particle size measurement: weighing 1g prepared by the method of the invention, adding 100ml of distilled water for emulsification, and measuring the particle size by a laser particle size analyzer. As a result: the particle sizes of examples 1 to 3 were in the range of 10 to 100nm, and were distributed more at 19nm, 25nm and 32 nm.

Gelling temperature and gelling time: the ointment of example 1 had a gel formation time of 70 seconds at 35℃, the ointment of example 2 had a gel formation time of 125 seconds at 34℃, and the ointment of example 3 had a gel formation time of 56 seconds at 37℃.

2) Skin irritation test

When the cream is applied on skin or mucosa surface, adverse reactions such as pain, red swelling or plague should not be caused.

Single application test: removing hair from two sides of 20 rats before administration, respectively coating the medicinal cream on the left hair removing area of the rats, coating the blank cream matrix on the right hair removing area as control, fixing with gauze, washing off the residual cream and blank cream matrix with warm water after administration, and observing local erythema and red swelling reaction, wherein the results show that the prescriptions 1-3 have no local erythema and red swelling reaction.

Multiple coating tests: respectively coating the medicinal cream of each prescription on the left hair removal area of a rat, coating the blank cream matrix of each prescription on the right hair removal area as a control, fixing with gauze, continuously coating the medicines, washing away the residual cream and the blank cream matrix with warm water after administration, observing whether the skin has edema and erythema, and continuously observing the skin condition for one week, wherein the results show that the prescriptions 1-3 have no red swelling, rash and blister.

3) Stability survey

And (3) centrifugal experiment: samples of each prescription are respectively taken and placed in a centrifuge tube, and are centrifuged at the rotating speed of 2500r/min, and whether the cream is layered or not and whether the medicine is precipitated or not are observed, which is detailed in table 1.

Cold and heat resistance test: taking samples of each formula, respectively placing into a sealed plastic box, and observing whether demulsification occurs in a refrigerator at-15 ℃ for 24 hours and a thermostat at 55 ℃ for 6 hours, wherein the detail is shown in Table 1.

Accelerated testing: samples of each prescription are respectively taken and placed in an environment with the temperature of (30 +/-2) ° C and the relative humidity of (60 +/-5)% to be respectively sampled at the end of 1, 2, 3 and 6 months to investigate the characters, the content change and the like, and whether rancidity, discoloration, layering and other phenomena exist is observed, and the details are shown in table 1.

Sample retention observation method: samples of each formula are taken and respectively put into a closed plastic box, and whether demulsification, oil leakage and the like occur or not is checked in half a year of storage at room temperature, and the details are shown in table 1.

Table 1 prescription test results table

The result shows that the preparation of the invention has reasonable prescription, good stable state after being stored for 6 months, and is excellent gel ointment.

(4) Rheological investigation of blank matrix

The apparent viscosity of the blank matrix of example 3 was measured at different temperatures using a rotary viscometer. Placing 10mL of gel to be measured in a sample tube with the inner diameter of 20mm, slowly heating to 40 ℃ at the speed of 1-2 ℃/min, selecting a suspension type rotor with a proper range to immerse the sample to the scale, and measuring the viscosity at different temperatures. Starting at 15 ℃, a viscosity value is recorded for each 1 ℃ rise in temperature, to the point where the viscometer rotor is out of range. The gel samples in each sample tube are subjected to parallel measurement for 3 times, the results are averaged, the viscosity coefficient of the gel is similar to that of 800 at a lower temperature, when the temperature is increased to be about 35 ℃, the viscosity of the gel is increased rapidly, the gel is changed from liquid to semisolid, and the viscosity reaches more than 1500.

Verification example 1: pharmacological and pharmacodynamic study on healing rate of wound surface

80 SD rats of about 150g are randomly divided into experimental groups 1, 2 and 3 and a blank group, the backs of the two groups of rats are subjected to unhairing treatment, after the skin is disinfected by 75% alcohol, 1 multiplied by 1cm of incision is respectively formed on the two sides of the back, the blank control group enables the rats to heal by themselves, the ointment of the experimental group in the embodiment 1-3 is smeared on the wound bottom surface, and the wound healing rate is recorded on days 3, 7 and 14 respectively. The results show that the healing rate of the wound surface is obviously improved after the ointment of the invention is applied, and the experimental results are shown in table 2:

TABLE 2 wound healing rates of rats of different treatment groups recorded at different time points

Verification example 2: hot plate method pain test for mice

The test method comprises the following steps: taking 19-20g of ICR female mice, using a hot plate pain measuring instrument to measure the time (seconds) required by the mice from putting the mice into a hot plate to licking the feet as the pain threshold value of the mice, discarding the mice when the mice licking the feet for less than 5 seconds or more than 30 seconds or jumping people, randomly dividing the qualified mice into 5 groups, 10 mice in each group, administering, treating groups 1, 2 and 3 by using the ointment of the invention of the embodiments 1, 2 and 3 respectively, and measuring the pain threshold values of 30, 60, 90 and 120 minutes after administration.

TABLE 3 Hot plate pain test results table

And (4) conclusion: the mouse hot plate method results show that the ointment of the invention has analgesic effect in each of the high, medium and low dose groups, and the low, medium and high dose groups have obvious effect and have significant difference compared with the blank group. The ointment of the invention has obvious analgesic effect in low, medium and high dosage groups.

The embodiments given above are preferable examples for implementing the present invention, and the present invention is not limited to the above-described embodiments. Any non-essential addition and replacement made by the technical characteristics of the technical scheme of the invention by a person skilled in the art belong to the protection scope of the invention.

Claims (8)

1. An ointment for clearing heat, cooling blood, stopping bleeding, diminishing swelling and promoting wound healing is prepared from medicinal dry paste powder and a matrix auxiliary material, and is characterized in that each 100g of the ointment comprises the following components in parts by weight: 5-15g of medicine dry paste powder, 5-11g of thickening agent, 15-20g of oil phase matrix, 10-20g of water phase matrix, 20-30g of surfactant, 0.1-0.5 part of preservative and the balance of water.

2. The ointment for clearing heat to cool blood, stopping bleeding to reduce swelling and promoting wound healing according to claim 1, is characterized in that the oil phase matrix is isopropyl myristate, the water phase matrix is one or more of polyethylene glycol 400 or glycerol, the preservative is one or more of ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate and sodium benzoate, the surfactant is one or more of tween 80 and polyoxyethylene castor oil, and the thickening agent is one or more of chitosan derivatives and β -sodium glycerophosphate.

3. The ointment for clearing heat and cooling blood, stopping bleeding and diminishing swelling and promoting wound healing as claimed in claim 2, wherein each 100g of the ointment comprises the following components, by weight, 5-15g of drug dry paste powder, 1-3g of chitosan derivative, 4-8g of β -sodium glycerophosphate, 15-20g of isopropyl myristate, 10-20g of polyethylene glycol 400 or glycerol, 5-20g of tween 8015, 5-10g of polyoxyethylene castor oil, 0.1-0.5 part of ethyl p-hydroxybenzoate, and the balance of water.

4. The ointment for clearing heat and cooling blood, stopping bleeding and diminishing swelling and promoting wound healing according to claim 1, is characterized in that the medicine dry ointment powder comprises the following raw material medicines in parts by weight: 50-80 parts of rheum officinale, 40-60 parts of coptis chinensis, 40-60 parts of pseudo-ginseng, 20-40 parts of angelica dahurica, 40-60 parts of donkey-hide gelatin, 30-55 parts of calcined dragon bone, 30-55 parts of rhizoma bletillae, 20-40 parts of vinegar myrrh, 30-55 parts of cuttlebone, 40-60 parts of madder, 10-20 parts of dragon's blood, 2-10 parts of pearl, 2-10 parts of borneol and 5-20 parts of liquorice.

5. The ointment for clearing heat and cooling blood, stopping bleeding and diminishing swelling and promoting wound healing according to claim 4, is characterized by comprising the following components in parts by weight: 65 parts of rhubarb, 50 parts of coptis chinensis, 50 parts of pseudo-ginseng, 31 parts of angelica dahurica, 50 parts of donkey-hide gelatin, 44 parts of calcined dragon bone, 44 parts of rhizoma bletillae, 31 parts of vinegar myrrh, 44 parts of cuttlebone, 50 parts of madder, 12 parts of dragon's blood, 4 parts of pearl, 4 parts of borneol and 11 parts of liquorice.

6. An ointment for clearing heat, cooling blood, stopping bleeding, eliminating swelling and promoting wound healing as claimed in claim 2 or 3, wherein the chitosan derivative can be one or more of chitosan lactate, chitosan hydrochloride, chitosan nitride, carboxymethyl chitosan, hydroxypropyl chitosan, chitosan acetate, chitosan propionate, chitosan succinate, chitosan glutarate, chitosan adipate, succinylated chitosan, and maleylated chitosan.

7. The ointment for clearing heat and cooling blood, stopping bleeding and diminishing swelling and promoting wound healing as claimed in claim 4, is characterized in that the medicinal dry paste powder consists of dry paste powder, superfine powder and borneol, and comprises the following steps:

1) mixing radix et rhizoma Rhei, Coptidis rhizoma, Notoginseng radix and radix Angelicae Dahuricae, adding 5-10 times of 70-85% ethanol, and soaking for 45-60 min; heating and refluxing the soaked mixture twice, wherein each time lasts for 1.5-3 hours, combining the alcohol extract, and filtering through a 200-mesh stainless steel net to obtain a filtrate for later use; adding 8-10 times of water into the dregs of the alcohol extraction, cuttlebone, bletilla striata, calcined dragon bone, madder and liquorice, decocting for 2 times, each time for 1-1.5 hours, combining the decoction, filtering through a 180-mesh stainless steel net, concentrating the filtrate to obtain clear paste with the relative density of 1.05-1.10, performing spray drying or reduced pressure concentration drying, adding the formula amount of donkey-hide gelatin, and crushing to obtain 120-mesh 180-mesh dispersed fine powder to obtain dry paste powder;

2) mixing Myrrha, Margarita and sanguis Draxonis, pulverizing, sieving with 100 mesh sieve to obtain coarse powder, micronizing, and sieving with 300 mesh sieve to obtain superfine powder with average particle diameter of 50 μm or less;

3) grinding Borneolum Syntheticum into fine powder for use.

8. The method for preparing an ointment for clearing heat and cooling blood, stopping bleeding and reducing swelling and promoting wound healing according to claim 3 is characterized by comprising the following steps:

1) dissolving polyethylene glycol 400 or glycerol in water, adding chitosan derivative, stirring to dissolve, dissolving β -sodium glycerophosphate in distilled water, stirring to dissolve, dropwise adding the above chitosan solution, continuously stirring and fully mixing, standing until bubbles disappear, then adding ethyl p-hydroxybenzoate, fully mixing with the dried extract powder at constant temperature of 85 ℃, stirring to dissolve, and adding water to the prescription amount to serve as a water phase;

2) mixing the above superfine powder with isopropyl myristate, and mixing at constant temperature of 75-90 deg.C to obtain oil phase;

3) adding tween 80 and polyoxyethylene castor oil into the oil phase, stirring, dissolving, slowly adding the water phase while stirring, grinding Borneolum with small amount of 95% ethanol, dissolving, adding into the matrix, stirring, cooling, and adding water to 100g to obtain cream.